Chronic early postnatal administration of ethylmalonic acid to rats causes behavioral deficit.
High concentrations of ethylmalonic acid (EMA) are found in tissues and biological fluids of patients affected by ethylmalonic encephalopathy (EE), as well as by deficiency of short-chain acyl-CoA dehydrogenase (SCAD) activity and other illnesses characterized by developmental delay and other neurological and muscular symptoms. The pathophysiological mechanisms responsible for the brain damage in these patients are virtually unknown. However, they may be due to the neurotoxic actions of EMA. Therefore, in the present work we investigated whether chronic exposure of EMA during early development (from 5th to 28th day of life) could alter the behavioral performance of adult rats in the Morris water maze (MWM) and elevated plus maze tasks. Control rats were treated with saline in the same volumes. We observed that adult rats pretreated with EMA presented impairment in the learning and memory in water maze task spending significantly less time in the training quadrant. However, chronic EMA administration did not affect rat performance in the elevated plus maze tasks, suggesting that anxiety-like behavior was not changed by EMA. We also evaluated the in vitro effect of EMA on lipoperoxidation and on creatine kinase (CK) activity in rat hippocampus and observed that this metabolite induced lipid peroxidation and diminished creatine kinase activity. The results provide evidence that early chronic EMA treatment induces long-lasting spatial behavioral deficit that may be possibly related to a secondary bioenergetics dysfunction and/or increase of free radical production caused by this organic acid.
Schuck
Patrícia Fernanda
PF
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Ferreira
Gustavo da Costa
Gda C
Viegas
Carolina Maso
CM
Tonin
Anelise Miotti
AM
Busanello
Estela Natacha Brandt
EN
Pettenuzzo
Leticia Ferreira
LF
Netto
Carlos Alexandre
CA
Wajner
Moacir
M
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000139:chemically induced / Q000503:physiopathology; D002478:Cells, Cultured; D003402:Creatine Kinase / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects* / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007279:Injections, Subcutaneous; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008314:Malonates / Q000008:administration & dosage / Q000633:toxicity*; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013053:Spectrophotometry; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors
D008314:Malonates; D017392:Thiobarbituric Acid Reactive Substances; C038080:ethylmalonic acid; D003402:Creatine Kinase